Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493994 | SCV000583078 | uncertain significance | not provided | 2017-05-22 | criteria provided, single submitter | clinical testing | The H745R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H745R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Fulgent Genetics, |
RCV002496899 | SCV002776771 | uncertain significance | Hypokalemic periodic paralysis, type 1; Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Familial hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16 | 2021-07-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002527107 | SCV003475657 | uncertain significance | Familial hyperkalemic periodic paralysis | 2023-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 745 of the SCN4A protein (p.His745Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 430303). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). |